- This project can be modified to suit Honours, PhD or Clinical students
All body cells have an absolute requirement for iron for growth, division and normal metabolic function. However, while iron is essential, it is also toxic when present in excess. It has been known for some time that an optimal supply of iron is important for a healthy immune system, but only in recent years has it been appreciated that maintaining an optimal iron level is critical for effective function of both the innate and adaptive immune pathways. Despite this there are still very few data to demonstrate how modulating iron levels in different classes of immune cells influences immune function in vivo.
The goal of this project is to selectively inactivate the expression of the key iron import protein DMT1 and the iron export protein FPN1 in various types of immune cells. These studies will allow us to either deplete or load these cells with iron respectively, and we can then investigate how these animals respond to various challenges, including challenge with pathogens.
In its simplest form, this project involved breeding mouse strains to generate the required cell type-specific knockouts of DMT1 and FPN1, then characterising both the iron phenotype of the resulting animals and their immune function. All the genetically modified mouse lines required for this project are currently available in-house at QIMR Berghofer. Once the animals have been generated, they will be characterised to make sure the anticipated gene inactivation has been effective. Both systemic iron levels and distribution will be studied, as well as the iron content of specific cell types. Flow cytometry will be used to evaluate the numbers of a range of specific immune system cells both at baseline, and in response to various insults that would normally produce a robust immune response.
Techniques to be used include mouse breeding and detailed phenotypic analysis, flow cytometry, immunohistochemistry, conventional biochemical, molecular and cell biology procedures, and a range of immune system assays.